DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application claims benefit to PCT/SG2022/050088 (filed 02/23/2022) and SG10202101791Y (filed 02/23/2021) and is acknowledged. The instant claims herein are examined using the effective filing date of 02/23/2021 for the basis of any prior art rejections.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 12/27/2023 and 05/29/2025 were properly filed in compliance with 37 CFR 1.97. Accordingly, the information disclosure statement(s) were considered.
Drawings
The drawings are objected to because the drawings recite “Figure” instead of “FIG.”. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities: the specification refers to the drawings as “Figure” instead of “FIG.”.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities: claim 1 recites, inter alia, “Method for the enzymatic ligation of a (poly)peptide with a cargo molecule, the method comprising the steps of: (i) providing at least one cargo molecule modified with a peptide tag and at least one poly(peptide) to be ligated to the cargo molecule . . .” (emphasis added). It is suggested that “poly(peptide)” should be amended to recite “(poly)peptide” for consistency. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the enzymatic ligation" in line 1. There is insufficient antecedent basis for this limitation in the claim. There is no previous recitation of any enzymatic ligation in the claim, thus the claim is indefinite. Please note that claims 2-15 are also indefinite for dependency on indefinite claim 1.
Claim 1 recites, inter alia, “Method for the enzymatic ligation of a (poly)peptide with a cargo molecule, the method comprising the steps of: (i) providing at least one cargo molecule modified with a peptide tag and at least one poly(peptide) to be ligated to the cargo molecule . . .” (emphasis added). It is unclear whether there is a difference between the “(poly)peptide” and “poly(peptide)” recited in the claims. For the purposes of compact patent prosecution, the examiner is interpreting “poly(peptide)” and “(poly)peptide” to mean the same thing (i.e., a (poly)peptide), as defined in the specification on pg. 13 of the specification, which recites “the term ‘(poly)peptide’ refers to peptides and polypeptides”. In short, the examiner is interpreting the phrase to mean polypeptide (long) or peptide (short).
Regarding claims 3, 12, and 13, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purposes of compact patent prosecution, the limitations proceeding the preferably language have been interpreted to be optional limitations of the claimed invention.
It is noted any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
Claim Interpretation
The examiner has interpreted claim 15, reciting “conjugates obtainable according to the method of claim 1” as a product-by-process limitation. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (see MPEP 2113).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 15 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lu et al. (Chemical strategies for the synthesis of peptide-oligonucleotide conjugates. Bioconjug Chem. 2010 Feb 17;21(2):187-202; in 12/27/2023 IDS; hereinafter “Lu”).
Lu teaches various peptide-oligonucleotide conjugates via chemical ligation techniques (see abstract, see Fig. 3, and 5-6). As interpreted above, the claimed conjugate has been interpreted as a product-by-process. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (see MPEP 2113). Thus, the peptide/oligonucleotide conjugates of Lu meet the claim limitation, such that the disclosure of Lu anticipates the claimed invention.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
First rejection
Claims 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Lu in view of Schmidt et al (Enzyme-mediated ligation technologies for peptides and proteins. Curr Opin Chem Biol. 2017 Jun;38:1-7. doi: 10.1016/j.cbpa.2017.01.017. Epub 2017 Apr 20; in 12/27/2023 IDS; hereinafter “Schmidt”).
Lu teaches chemical strategies for synthesis and development of efficient and reproducible methods for convenient preparation of covalently linked peptide-oligonucleotide conjugates (POCs) (see title and abstract), including chemical ligation and enzymatic approaches to creating nucleopeptide POCs (see Fig. 3, 5, and 6; pg. 197; a method of ligation of a (poly)peptide as in claim 1). Lu teaches taking oligonucleotides (i.e., cargo molecule) peptides and conjugating via chemical linkages and bonding, like keto-oxime bonds, oxime bonds, glyoxylic oxime bond, etc. (see Fig. 3-6).
Lu does not explicitly teach that the cargo molecule is modified with a peptide tag, wherein the peptide tag and/or the (poly)peptide comprises a ligation motif for a peptide ligase; and (ii) contacting the cargo molecule and the poly(peptide) with a peptide ligase that ligates the peptide tag with the (poly)peptide via the ligation motif.
However, Schmidt teaches enzyme-mediated ligation technologies for peptides and proteins (see title, abstract). Schmidt explicitly teaches enzymatic strategies using ligases and peptide tags such as sortase, butelase, peptiligase or omniligase generally feature excellent chemoselectivity, therefore making them valuable tools for protein and peptide chemists (see abstract). Schmidt teaches ligase mediated strategies using sortase and butelase 1, where the polypeptide/peptides contain a sortase or butelase-1 ligation motif (as in claim 1; see light gray rectangle in Fig. 1 and 2 reproduced below) and contacting the peptide with the ligase to ligate the tag with a peptide via the sortase or butelase-1 ligation motifs (as in claim 1; see black and grey ligation catalyzed product in Fig. 1 and 2 below).
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Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the method of making peptide and oligonucleotide conjugates as taught by Lu with the enzymatic ligation techniques as taught by Schmidt to arrive at the claimed invention. One of ordinary skill would have been motivated to make the modification because Schmidt explicitly teaches that enzymatic strategies using ligases such as sortase, butelase, peptiligase or omniligase generally feature excellent chemoselectivity, and are valuable tools for protein engineering, chemoselective labelling and macrocyclization of peptides and proteins (see pg. 1, col 1).
Regarding claim 2, it would have been prima facie obvious to include a peptide tag (such as the one taught by Schmidt in the oligonucleotide as taught by Lu for the same reasons as set forth above.
Regarding claim 3, Schmidt teaches, e.g., LPXTG sortase peptide tag, which is 5 amino acids long (i.e., up to 10 amino acids).
Regarding claim 4, Lu teaches using a cyclodecapeptide scaffold as a key intermediate to anchor the carbohydrate cluster and the ON through sequential oxime bond formation (see pg. 190, col 1).
Regarding claim 5, Schmidt teaches the ligation motif is on the C-terminus (see Fig. 1 above).
Regarding claim 6, Schmidt teaches using sortase and butelase (see above).
Regarding claim 7-8, Lu teaches the cargo molecule is oligonucleotides.
Regarding claim 9 and 10, Lu teaches conjugation of peptide to oligonucleotide (ON) mostly occurs at 5′- or 3′-ends of the ON and on 2′-position of the ribose sugar and nucleobases (see pg. 187, col 2).
Regarding claim 11-13, Lu teaches using various oligonucleotide analogues including 2′-O-carboxymethyl ON (as in claim 11) that were obtained by using a novel uridine 3′-phosphoramidite building block (as in claim 12), where the resulting ONs were then efficiently conjugated on a solid support under normal peptide coupling conditions to various amines or to the N-termini of small peptides to give pure products in good yield. (pg. 189, col 1). Lu also teaches using phosphoramidite derivatives capable of introducing aldehyde and glyoxylic aldehyde precursors at 5′-end of the ON. The phosphoramidite derivative #4 depicted in Fig. 5 (which reads on claimed structure (A5)) was prepared in two straight steps starting from 1,2,6-hexane triol and incorporated at the 5′-end of the ON during the solid-phase ON synthesis using the routine coupling procedure (see screenshot below).
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Regarding claim 14, it would have been prima facie obvious to one of ordinary skill at the time of filing to combine ligation motifs of Schmidt for peptide ligase to arrive at the claimed invention. It is prima facie obvious to combine two compositions (the ligation motifs) each of which is taught by the prior art to be useful for the same purpose (advantageous ligation of polypeptides), in order to form a third composition to be used for the very same purpose. “The idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (see MPEP 2144.06).
Regarding claim 15, Lu and Schmidt, in combination, teach conjugates obtained by the claimed method.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill at the time of filing, especially in the absence of evidence to the contrary.
Conclusion
NO CLAIMS ALLOWED.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
AU-719029-B2: discloses modification of (poly)peptides to facilitate their purification comprises the insertion of at least one specific cleavable amino acid (aa) at the end of the (poly)peptide chain during synthesis and protecting any AAs within the polypeptide sequence that are the same as the specific aa against cleavage, in order to allow for specific cleavage precisely at the specific inserted cleavable aa(s). Also claimed is a process for the preparation of purified (poly)peptides using the above modification method, the process comprising: (a) synthesising the desired (poly)peptide; (b) adding at least one specific cleavable aa at the end of the (poly)peptide, while protecting the same aa(s) present within the (poly)peptide against cleavage; (c) elongating the (poly)peptide with aa(s) comprising a tag sequence; (d) purifying the elongated (poly)peptide by means of a tag-specific purification method (see abstract, claims, throughout).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGIANA C REGLAS whose telephone number is (571)270-0995. The examiner can normally be reached M-Th: 8:00am-2:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/G.C.R./Examiner, Art Unit 1651
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672